Dataset Information

IBD Genetic Risk Profile in Healthy First-Degree Relatives of Crohn's Disease Patients.

ABSTRACT: Family history provides important information on risk of developing inflammatory bowel disease [IBD], and genetic profiling of first-degree relatives [FDR] of Crohn's disease [CD]- affected individuals might provide additional information. We aimed to delineate the genetic contribution to the increased IBD susceptibility observed in FDR.N = 976 Caucasian, healthy, non-related FDR; n = 4997 independent CD; and n = 5000 healthy controls [HC]; were studied. Genotyping for 158 IBD-associated single nucleotide polymorphisms [SNPs] was performed using the Illumina Immunochip. Risk allele frequency [RAF] differences between FDR and HC cohorts were correlated with those between CD and HC cohorts. CD and IBD genetic risk scores [GRS] were calculated and compared between HC, FDR, and CD cohorts.IBD-associated SNP RAF differences in FDR and HC cohorts were strongly correlated with those in CD and HC cohorts, correlation coefficient 0.63 (95% confidence interval [CI] 0.53 - 0.72), p = 9.90 x 10(-19). There was a significant increase in CD-GRS [mean] comparing HC, FDR, and CD cohorts: 0.0244, 0.0250, and 0.0257 respectively [p < 1.00 x 10(-7) for each comparison]. There was no significant difference in the IBD-GRS between HC and FDR cohorts [p = 0.81]; however, IBD-GRS was significantly higher in CD compared with FDR and HC cohorts [p < 1.00 x 10(-10) for each comparison].FDR of CD-affected individuals are enriched with IBD risk alleles compared with HC. Cumulative CD-specific genetic risk is increased in FDR compared with HC. Prospective studies are required to determine if genotyping would facilitate better risk stratification of FDR.

SUBMITTER: Kevans D

PROVIDER: S-EPMC5007582 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

IBD Genetic Risk Profile in Healthy First-Degree Relatives of Crohn's Disease Patients.

Kevans David D Silverberg Mark S MS Borowski Krzysztof K Griffiths Anne A Xu Wei W Onay Venus V Paterson Andrew D AD Knight Jo J Croitoru Ken K

Journal of Crohn's & colitis 20151028 2

<h4>Background</h4>Family history provides important information on risk of developing inflammatory bowel disease [IBD], and genetic profiling of first-degree relatives [FDR] of Crohn's disease [CD]- affected individuals might provide additional information. We aimed to delineate the genetic contribution to the increased IBD susceptibility observed in FDR.<h4>Methods</h4>N = 976 Caucasian, healthy, non-related FDR; n = 4997 independent CD; and n = 5000 healthy controls [HC]; were studied. Genoty ...[more]

PMID: 26512135

Similar Datasets

Project description:ImportanceCholesteatoma in the middle ear is not regarded as a hereditary disease, but case reports of familial clustering exist in the literature, as well as observed familial cases in the clinical work. However, the knowledge regarding cholesteatoma as a hereditary disease is lacking in the literature.ObjectiveTo assess the risk of cholesteatoma in individuals with a first-degree relative surgically treated for the same disease.Design, setting, and participantsIn this nested case-control study in the Swedish population between 1987 and 2018 of first-time cholesteatoma surgery identified from the Swedish National Patient Register, 2 controls per case were randomly selected from the population register through incidence density sampling, and all first-degree relatives for cases and controls were identified. Data were received in April 2022, and analyses were conducted between April and September 2022.ExposureCholesteatoma surgery in a first-degree relative.Main outcomes and measuresThe main outcome was first-time cholesteatoma surgery. The association between having a first-degree relative with cholesteatoma and the risk of cholesteatoma surgery in the index persons was estimated by odds ratios (ORs) and 95% CIs through conditional logistic regression analysis.ResultsBetween 1987 and 2018, 10 618 individuals with a first-time cholesteatoma surgery (mean [SD] age at surgery, 35.6 [21.5] years; 6302 [59.4%] men) were identified in the Swedish National Patient Register. The risk of having a cholesteatoma surgery was almost 4 times higher in individuals having a first-degree relative surgically treated for the disease (OR, 3.9; 95% CI, 3.1-4.8), but few cases were exposed overall. Among the 10 105 cases with at least 1 control included in the main analysis, 227 (2.2%) had at least 1 first-degree relative treated for cholesteatoma, while the corresponding numbers for controls were 118 of 19 553 control patients (0.6%). The association was stronger for individuals under the age of 20 years at first surgery (OR, 5.2; 95% CI, 3.6-7.6) and for a surgery involving the atticus and/or mastoid region (OR, 4.8; 95% CI, 3.4-6.2). There was no difference in the prevalence of having a partner with cholesteatoma between cases and controls (10 cases [0.3%] and 16 controls [0.3%]; OR, 0.92; 95% CI, 0.41-2.05), which implies that increased awareness does not explain the association.Conclusions and relevanceIn this Swedish case-control study using nationwide register data with high coverage and completeness, the findings suggest that the risk of cholesteatoma in the middle ear is strongly associated with a family history of the condition. Family history was nevertheless quite rare and can therefore only explain a limited number of all cases; these families could be an important source for information regarding the genetic background for cholesteatoma disease.

Project description:BackgroundAutoimmune disease prevention requires tools to assess an individual's risk of developing a specific disease. One tool is disease-associated autoantibodies, which accumulate in an asymptomatic preclinical period. However, patients sometimes exhibit autoantibodies associated with a different disease classification. When and how these alternative autoantibodies first appear remain unknown. This cross-sectional study characterizes alternative autoimmunity, and associated genetic and environmental factors, in unaffected first-degree relatives (FDRs) of patients, who exhibit increased future risk for the same disease.MethodsSamples (n = 1321) from disease-specific autoantibody-positive (aAb+) systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and type 1 diabetes (T1D) patients; and unaffected aAb+ and autoantibody-negative (aAb-) SLE and RA FDRs were tested for SLE, RA, and T1D aAbs, as well as anti-tissue transglutaminase, anti-cardiolipin and anti-thyroperoxidase. FDR SLE and RA genetic risk scores (GRS) were calculated.FindingsAlternative autoimmunity occurred in SLE patients (56%) and FDRs (57·4%), RA patients (32·6%) and FDRs (34·8%), and T1D patients (43%). Expanded autoimmunity, defined as autoantibodies spanning at least two other diseases, occurred in 18·5% of SLE patients, 16·4% of SLE FDRs, 7·8% of RA patients, 5·3% of RA FDRs, and 10·8% of T1D patients. SLE FDRs were more likely to have alternative (odds ratio [OR] 2·44) and expanded (OR 3·27) autoimmunity than RA FDRs. Alternative and expanded autoimmunity were associated with several environmental exposures. Alternative autoimmunity was associated with a higher RA GRS in RA FDRs (OR 1·41), and a higher SLE GRS in aAb+ RA FDRs (OR 1·87), but not in SLE FDRs.InterpretationAutoimmunity commonly crosses disease-specific boundaries in systemic (RA, SLE) and organ-specific (T1D) autoimmune diseases. Alternative autoimmunity is more common in SLE FDRs than RA FDRs, and is influenced by genetic and environmental factors. These findings have substantial implications for preclinical disease pathogenesis and autoimmune disease prevention studies. FUND: NIH U01AI101981, R01AR051394, U19AI082714, P30AR053483, P30GM103510, U54GM104938, U01AI101934, R01AI024717, U01AI130830, I01BX001834, & U01HG008666.

Dataset Information

IBD Genetic Risk Profile in Healthy First-Degree Relatives of Crohn's Disease Patients.

Publications

IBD Genetic Risk Profile in Healthy First-Degree Relatives of Crohn's Disease Patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets